Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

Stephanie K. Dougan, Joseph Ashour, Roos A. Karssemeijer, Maximilian W. Popp, Ana M. Avalos, Marta Barisa, Arwen F. Altenburg, Jessica R. Ingram, Juan Jose Cragnolini, Chunguang Guo, Frederick W. Alt, Rudolf Jaenisch, Hidde L. Ploegh

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection. However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response.

Original languageEnglish
Pages (from-to)406-409
Number of pages4
JournalNature
Volume503
Issue number7476
DOIs
StatePublished - 2013
Externally publishedYes

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